BIOPHYSICAL THEORY AND MODELING |
Understanding the molecular basis for differential binding of integrins to collagen and gelatin
Muhammad H Zaman 1*
1 UT Austin
* To whom correspondence should be addressed. E-mail: mhzaman{at}mail.utexas.edu.
Submitted on September 14, 2006
Revised on October 20, 2006
Accepted on 20 October 2006
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Abstract |
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ntegrin-mediated cell adhesion plays a central role in cell migration and signaling. Overexpression of integrins is also associated with cancer invasion and metastasis. While a number of problems in integrin-matrix interactions have been studied in detail, the molecular specificity, which increases integrin adhesion to native collagen but results in poor integrin-gelatin interaction is not understood. In this paper, we study the role of individual amino acids in integrin-collagen and integrin-gelatin interactions using long-term (>100ns) molecular simulations. The results, which are force field independent, show that denatured collagen induces helical conformations in integrin amino acids and significantly reduces the PP-II content, which stabilizes the integrin-collagen interactions. Our simulations provide a possible explanation of the molecular specificity in integrin binding and suggests new targets for regulating integrin-mediated invasion and metastasis.
Key Words:
Cell Adhesion, Collagen, Gelatin, Integrin, Molecular Dynamics
